First Online: 18 November 2013Received: 24 March 2013Accepted: 05 November 2013

Abstract

IntroductionAlthough IL-1β is believed to be crucial in the pathogenesis of osteoarthritis OA, the IL-1β blockade brings no therapeutic benefit in human OA and results in OA aggravation in several animal models. We explored the role of a cytokine signaling 1 SOCS1 suppressor as a regulatory modulator of IL-1β signaling in chondrocytes.

MethodsCartilage samples were obtained from patients with knee OA and those without OA who underwent surgery for femur-neck fracture. SOCS1 expression in cartilage was assessed with immunohistochemistry. IL-1β-induced SOCS1 expression in chondrocytes was analyzed with quantitative polymerase chain reaction and immunoblot. The effect of SOCS1 on IL-1β signaling pathways and the synthesis of matrix metalloproteinases MMPs and aggrecanase-1 was investigated in SOCS1-overexpressing or -knockdown chondrocytes.

ResultsSOCS1 expression was significantly increased in OA cartilage, especially in areas of severe damage P ConclusionsOur results show that SOCS1 is induced by IL1-β in OA chondrocytes and suppresses the IL-1β-induced synthesis of matrix-degrading enzymes by inhibiting IL-1β signaling at multiple levels. It suggests that the IL-1β-inducible SOCS1 acts as a negative regulator of the IL-1β response in OA cartilage.

AbbreviationsADAMTS-4Aggrecanase-1, a disintegrin and metalloproteinase with thrombospondin motifs 4

CIS-1Cytokine-inducible SH2-containing protein 1

DMEMDulbecco modified Eagle medium

ELISAEnzyme-linked immunosorbent assay

ERKExtracellular-signal-regulated kinase

FBSFetal bovine serum

GAPDHGlyceraldehyde-3-phosphate dehydrogenase

HACHuman articular chondrocyte

IFNInterferon

IHCImmunohistochemistry

IPImmunoprecipitation

IκBInhibitor of nuclear factor κB

JAKJanus kinase

JNKc-Jun N-terminal kinase

MAPKMitogen-activated protein kinase

MMPMatrix metalloproteinase

NF-κBNuclear factor κB

OAOsteoarthritis

OARSIOsteoArthritis Research Society International

RT-PCRReverse transcription polymerase chain reaction

shRNASmall hairpin RNA

SOCSSuppressor of cytokine signaling

STATSignal transducer and activator of transcription

TAK1Transforming growth factor-β activated kinase 1

TIMPTissue inhibitor of metalloproteinase

TNFTumor necrosis factor.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4381 contains supplementary material, which is available to authorized users.